ArticleBiophysical journal2019
Size Matters: Ryanodine Receptor Cluster Size Heterogeneity Potentiates Calcium Waves.
Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Novel Ca2+ wave mechanisms in cardiac myocytes revealed by multiscale Ca2+ release model.The Journal of general physiology · 2025Article
- Positive feedback between RyR phosphorylation and CaBiophysical journal · 2025Article
- Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes.iScience · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells.Cells · 2024Article
- CaPhysiological reviews · 2024Review
- Clustering properties of the cardiac ryanodine receptor in health and heart failure.Journal of molecular and cellular cardiology · 2023Review
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- CaJournal of molecular and cellular cardiology · 2023Article
- Unveiling the intricacies of intracellular CaBiophysical journal · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- The role of subunit cooperativity on ryanodine receptor 2 calcium signaling.Biophysical journal · 2023Article
- Biological noise is a key determinant of the reproducibility and adaptability of cardiac pacemaking and EC coupling.The Journal of general physiology · 2022Review
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression.Journal of molecular and cellular cardiology · 2022Article
- Increasing SERCA function promotes initiation of calcium sparks and breakup of calcium waves.The Journal of physiology · 2021Article
- NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology.Antioxidants (Basel, Switzerland) · 2021Review
- Simulating cardiac CaPflugers Archiv : European journal of physiology · 2021Article
- Nanoscale Organization, Regulation, and Dynamic Reorganization of Cardiac Calcium Channels.Frontiers in physiology · 2021Review
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Authors and funding
5 authors.
Funding
Abstract
Ryanodine receptors (RyRs) mediate calcium (Ca)-induced Ca release and intracellular Ca homeostasis. In a cardiac myocyte, RyRs group into clusters of variable size from a few to several hundred RyRs, creating a spatially nonuniform intracellular distribution. It is unclear how heterogeneity of RyR cluster size alters spontaneous sarcoplasmic reticulum (SR) Ca releases (Ca sparks) and arrhythmogenic Ca waves. Here, we tested the impact of heterogeneous RyR cluster size on the initiation of Ca waves. Experimentally, we measured RyR cluster sizes at Ca spark sites in rat ventricular myocytes and further tested functional impacts using a physiologically detailed computational model with spatial and stochastic intracellular Ca dynamics. We found that the spark frequency and amplitude increase nonlinearly with the size of RyR clusters. Larger RyR clusters have lower SR Ca release threshold for local Ca spark initiation and exhibit steeper SR Ca release versus SR Ca load relationship. However, larger RyR clusters tend to lower SR Ca load because of the higher Ca leak rate. Conversely, smaller clusters have a higher threshold and a lower leak, which tends to increase SR Ca load. At the myocyte level, homogeneously large or small RyR clusters limit Ca waves (because of low load for large clusters but low excitability for small clusters). Mixtures of large and small RyR clusters potentiates Ca waves because the enhanced SR Ca load driven by smaller clusters enables Ca wave initiation and propagation from larger RyR clusters. Our study suggests that a spatially heterogeneous distribution of RyR cluster size under pathological conditions may potentiate Ca waves and thus afterdepolarizations and triggered arrhythmias.
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